comparing urinary biomarkers of exposure to polycyclic aromatic hydrocarbons

133 Pages·2008·0.87 MB·English

COMPARING URINARY BIOMARKERS OF EXPOSURE TO
POLYCYCLIC AROMATIC HYDROCARBONS

Jon Russell Sobus

A dissertation submitted to the faculty of the University of North Carolina at Chapel Hill in
partial fulfillment of the requirements for the degree of Doctor of Philosophy in the
department of Environmental Sciences and Engineering

Chapel Hill
2008

Approved by:

Advisor: Professor Stephen M. Rappaport

Professor Lawrence L. Kupper

Professor Leena Nylander-French

Professor Ivan Rusyn

Professor James A. Swenberg
ABSTRACT

JON RUSSELL SOBUS: Comparing Urinary Biomarkers of Exposure to Polycyclic
Aromatic Hydrocarbons
(Under the direction of Stephen M. Rappaport)

Polycyclic aromatic hydrocarbons (PAHs), which consist of two or more fused aromatic
rings, are ubiquitous products of combustion. These compounds are found in wood and
tobacco smoke, engine (particularly diesel) exhausts, and in numerous workplaces, including
those producing coke and aluminum and those processing hot asphalt. Because some PAHs
are potent carcinogens, it is important to assess the levels of exposure to these compounds
that are received by workers and the general public. However, PAHs are difficult to measure
in the environment because they exist in both the gas phase and the particulate phase, and the
carcinogenic particle-bound compounds are present at very low concentrations. In contrast,
the smaller vapor-phase PAHs are more abundant in the environment and produce a host of
urinary products that can be used as biomarkers of exposure. Here we consider the
hypothesis that urinary biomarkers of naphthalene (a 2-ring compound) and phenanthrene (a
3-ring compound) can be used as measures of exposure to total PAHs. We test this
hypothesis in three distinct phases of research. First, we determine the predictive value of
airborne naphthalene and phenanthrene as measures of exposure to diesel exhaust in a
controlled chamber study. Second, we determine the predictive value of urinary levels of
naphthalene and phenanthrene as measures of occupational exposure to diesel exhaust,
asphalt emissions, and coke-oven emissions. And finally, we develop statistical models of
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urinary biomarkers of naphthalene and phenanthrene in asphalt-exposed workers to
determine effects of particulate PAH levels in air and on the skin, job categories and tasks,
and physiological factors that might affect the uptake and elimination of these compounds.
Overall, this research demonstrates that urinary biomarkers of naphthalene and phenanthrene
can be used as measures of exposure to total PAHs in air and on the skin.

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This dissertation is dedicated to my parents, John and Doris Sobus, and my wife, Ryan.

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ACKNOWLEDGEMENTS

I thank my advisor Steve Rappaport for his continued support, guidance, and
friendship. Steve's influence on my professional growth over these past years is
immeasurable. Thanks to my committee members, Dr. Lawrence Kupper, Dr. Leena
Nylander-French, Dr. Ivan Rusyn, and Dr. James Swenberg, for their encouragement, helpful
ideas and suggestions, and belief in my ability to succeed. Thanks to Joachim Pleil for his
insight and expertise, sense of humor, generosity, and unwavering dedication to his friends
and colleagues. Thanks to Suramya Waidyanatha for teaching me everything I know about
analytical chemistry, and for setting a terrific example of excellence in our lab. Thanks to
my labmates, fellow students, and colleagues, Bill Funk, Sung Kim, David Kim, Christina
Kim, Yu-Sheng Lin, Renan Wu, Berrin Serdar, Alistair Henderson, Chris Trent, Russell
Bowen, Andrew Lindstrom, Peter Egeghy, Melissa Troester, Heidi Hubbard, and Frank
Onyemauwa, for their helpful conversations and friendships. Thanks to my collaborators,
specifically Dr. Michael Madden, Dr. Michael McClean, Dr. Robert Herrick, Dr. Eric
Garshick, Dr. Thomas Smith, and Dr. Yulix Zheng without whom this work would not have
been possible. Thanks to Dr. Myriam Medina-Vera, Dr. Allan Vette, Dr. Hunter Daughtrey,
Dr. Nicole Tulve, Dr. Linda Sheldon, Jon Berntsen, and Karen Oliver for their assistance
with the controlled chamber study. Thanks to the faculty and staff of the Environmental
Sciences and Engineering Department and the Biostatistics Department, specifically Jack
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Whaley, Melody Levy, Robin Whitley, Vera Bennett, Debbie Quach, Dr. Michael Aiken, Dr.
Donald Fox, Dr. David Leith, Dr. Michael Flynn, Richard Kamens, Dr. Howard Weinberg,
Dr. Louise Ball, Dr. Gunnar Boysen, James Wallace, and Randy Goodman, for their advice
and assistance. Finally, thanks to my Mom and Dad, my Wife, my Brother and Sister, my
Aunt and Uncle, my Godfather, Dr. Elichia Venso, and the rest of my family and friends for
always believing in me and supporting me along the way.
This work was supported by the National Institute of Environmental Health Sciences
through training grant T32ES07018 and research grants P42ES05948 and P30ES10126, and
by the Environmental Protection Agency through the Student Services Contracts Program.

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TABLE OF CONTENTS

LIST OF TABLES……………………………………………………………………….. xi

LIST OF FIGURES…………………………………………………………………….... xii

LIST OF ABBREVIATIONS AND SYMBOLS…………………………….................. xiv

1. Background and Significance………………………………………………….... 1

1.1. PAHs……………………………………………………………………..... 1

1.1.1. Occurrence and health effects………………….………………..... 1

1.1.2. Metabolism of PAHs……………………………………………..... 3

1.1.3. PAH exposure assessment………………………………………..... 6

1.1.4. Biomarkers of PAH exposure…………………………………….... 7

1.2. Diesel exhaust…………………………………………………………....... 9

1.3. Asphalt…………………………………………………………………....... 11

1.4. Specific goals of this project……………………………………………..... 12

2. Paper I. Identification of Surrogate Measures of Diesel Exhaust Exposure
in a Controlled Chamber Study [Sobus, J.R., Pleil, J.D., Madden, M.C.,
Funk, W.E., Hubbard, H.F., Rappaport, S.M., submitted to Environmental
Science and Technology, March, 2008.]……………………………………………….... 14

2.1. Abstract…………………………………………………………………..... 14

2.2. Introduction……………………………………………………………….. 15

2.3. Methods……………………………………………………………………. 16
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2.3.1. Study design………………………………………………………... 16

2.3.2. Collection and analysis of volatile aromatic
compounds and 2-4 ring PAHs………………………………….... 17

2.3.3. Collection and analysis of particle-bound PAHs………………….. 20

2.3.4. Collection and analysis of OC, EC, and PM2.5………………….... 21

2.3.5. Statistical methods……………………………………………….... 22

2.4. Results and Discussion…………………………………………………… 22

2.4.1. Volatile aromatics and PAHs in DE and purified air……………... 22

2.4.2. Nap and Phe as surrogates for DE exposures…………………….. 26

2.4.3. Variability assessment for Nap and Phe…………………………... 28

2.4.4. Correlations among surrogate measures of DE exposure...………. 30

2.4.5. Concluding remarks……………………………………………….. 33

3. Paper II. Urinary Naphthalene and Phenanthrene as Biomarkers of
Occupational Exposure to Polycyclic Aromatic Hydrocarbons [Sobus, J.R.,
Waidyanatha, S., McClean, M.D., Herrick, R.F., Smith, T.J., Garshick, E.,
Laden, F., Hart, J.E., Zheng, Y., Rappaport, S.M., submitted to Occupational
and Environmental Medicine; provisional acceptance, June 2008.] ............................. 34

3.1. Abstract……………………………………………………………………. 34

3.2. Introduction………………………………………………………………. 35

3.3. Methods……………………………………………………………………. 37

3.3.1. Chemicals and supplies……………………………………………..37

3.3.2. Sources of urine samples and published air measurements……….. 37

3.3.3. Analysis of urinary naphthalene and phenanthrene……………….. 39

3.3.4. Statistical analyses………………………………………………… 40

3.4. Results and discussion…………………………………………………….. 42
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3.4.1. Effects of job category on urinary analyte levels………………….. 42

3.4.2. Background-adjusted levels of urinary naphthalene
and phenanthrene………………………………………………….. 44

3.4.3. Relationships between urinary levels of naphthalene and
phenanthrene......................................................................................45

3.4.4. Relationships between air levels of naphthalene,
phenanthrene, and total PAHs………………………………….......48

3.5. Conclusions……………………………………………………………….. 52

4. Paper III. Analysis of Urinary Biomarkers of Asphalt Exposure Using
Mixed Models [Sobus, J.R., McClean, M.D., Herrick, R.F., Waidyanatha,
S., Onyemauwa, F., Kupper, L.L., Rappaport, S.M., to be submitted to Annals
of Occupational Hygiene]………………........................................................................... 53

4.1. Abstract…………………………………………………………………….. 53

4.2. Introduction……………………………………………………………….. 54

4.3. Methods……………………………………………………………………. 56

4.3.1. Study population and design……………………………………….. 56

4.3.2. Analysis of urinary naphthalene and phenanthrene……………….. 57

4.3.3. Analysis of urinary PAH metabolites………………………………. 57

4.3.4. Statistical methods…………………………………………………. 58

4.4. Results……………………………………………………………………... 59

4.4.1. Descriptive statistics and correlation analysis for
urinary analytes…………………………………………………..... 59

4.4.2. Effects of work group and sample type on urinary
analyte levels……………………………………………………...... 62

4.4.3. Linear mixed-effects models for urinary analytes…………………. 62

4.5. Discussion………………………………………………………………..... 67

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5. Paper IV. Biomarkers of Naphthalene, Phenanthrene, and Pyrene are
Predictors of Particulate Exposures to Polycyclic Aromatic Compounds in Asphalt-
Exposed Workers [Sobus, J.R., McClean, M.D., Herrick, R.F., Waidyanatha, S.,
Nylander-French, L., Kupper, L.L., Rappaport, S.M., to be submitted to Annals of
Occupational Hygiene]........................................................................................................ 72

5.1. Abstract………………………………………………………………….... 72

5.2. Introduction……………………………………………………………..... 73

5.3. Methods…………………………………………………………………..... 76

5.3.1 Subjects and air and urine measurements………………………… 76

5.3.2. Statistical analyses………………………………………………... 77

5.4. Results…………………………………………………………………....... 80

5.4.1. Postshift urine samples…………………………………………..... 80

5.4.2. Bedtime urine samples…………………………………………...... 82

5.4.3. Morning urine samples…………………………………………..... 83

5.5. Discussion………………………………………………………………..... 88

6. Discussion and Conclusions……………………………………………………... 96

6.1. Summary and conclusions……………………………………………....... 96

6.2. Significance of this study………………………………………………..... 98

6.3. Strengths and weaknesses of this study………………………………....... 100

6.4. Suggestions for future research………………………………………....... 102

REFERENCES..................................................................................................................... 105

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